PURPOSE: To study the efficacy of adding vancomycin in irrigating solutions, in comparison to topical antibiotic given preoperatively for a day, during phacoemulsification, in reducing the anterior chamber (AC) contamination.SETTINGS AND DESIGN: This was a prospective, interventional, hospital-based study.MATERIALS AND METHODS: This was a study involving 400 eyes of 400 paitens, undergoing routine phacoemulsification between January 2004 and June 2006. The patients were non-randomly assigned to two groups: Group 1 included 180 patients, who received topical ciprofloxacin eye-drops (four-hourly) for a day preoperatively and Group 2 included 220 patients, who underwent phacoemulsification with vancomycin (20 microg/ml) in the irrigating solution. Anterior chamber aspirate obtained at the end of the surgery was sent for microbial workup. The number of positive cultures in both the groups was determined.STATISTICAL ANALYSIS: This was performed using Chi-square test.RESULTS: Aqueous samples showed microbial growth in 38 (21.1%) out of 180 eyes in Group 1 and in 17 (7.7%) out of 220 eyes in Group 2 ( P = 0.001). Coagulase-negative staphylococcus was the most common organism in both the groups. Aqueous samples from four eyes in group 1 showed multiple organisms, while none of the sample from group 2 showed more than one organism. None of the eyes in either group showed fungal contamination. One patient in Group 1 developed endophthalmitis, and the causative organism was Alcaligenes faecalis. All patients were followed up for a minimum of six months (range: 6 to 14 months and mean: 9.3 months).CONCLUSION: Addition of vancomycin in irrigating solutions is more efficacious in reducing AC contamination in comparison to topical antibiotic administered a day preoperatively.

Postoperative endophthalmitis is a rare but devastating
complication of cataract surgery and remains one of the most
feared problems following intraocular surgeries. Although the
frequency of endophthalmitis has declined over the years, most
studies still report an incidence between 0.07% and 0.1%.1-4 Some recently concluded studies have shown that intracameral
injections of cefuroxime administered at the time of surgery5
or the use of subconjunctival antibiotics6 significantly reduces
the risk of developing endophthalmitis after cataract surgery.
However, use of intracameral cefuroxime has been associated
with toxic anterior segment syndrome,7 anaphylactic reactions8,9
and increased incidence of cystoid macular edema,10 thus
benefit should be weighed against side-effects.

Topical antibiotics can be used preoperatively for one
to three days to reduce the load of microorganisms in the
conjunctival flora, thus minimizing the anterior chamber
(AC) contamination.11,12 Antibiotics are being added
to the irrigating solution while performing cataract surgery, as a
prophylaxis against persistence of the organisms entering in
the AC. A recently published study had shown that antibiotics
(vancomycin and gentamicin) in irrigating fluids can be used
to decrease AC contamination.13

The reduction in intraocular contamination during
phacoemulsification is essential to prevent endophthalmitis.14-16 The aim of this prospective study was to compare the efficacy
in reducing the AC contamination between preoperative topical
0.3% ciprofloxacin eye-drops and addition of vancomycin
in a concentration of 20 µg/ml in the irrigating solution by
comparing the number of positive postoperative intraocular
cultures in both groups.

Materials and Methods

Patients undergoing routine phacoemulsification cataract
surgery between January 2004 and June 2006, more than
25 years of age and ready to give written informed consent
and not falling in the exclusion criteria were recruited in this
study. Ethical committee clearance was obtained. The exclusion
criteria were:

The patient having undergone prior intraocular surgery,

The patient having received any topical or systemic
antibiotics within 10 days prior to the enrollment into this
study,

Any source of local or systemic infection,

Evidence of any systemic disease,

The patient who required additional procedure along with
phacoemulsification,

The patient not ready to give consent for enrollment into
the study.

The patients were non-randomly assigned to two groups: 1
and 2. Patients enrolled in the study during the initial
15 months of the study were included in Group 1, while the
patients getting enrolled in the later 15 months of the study
were enrolled in Group 2. Group 1 included patients who
received topical 0.3% ciprofloxacin (Ciplox-0.3%, Cipla Ltd.)
eye-drops (four-hourly) for a day preoperatively but did not
receive vancomycin (VanSafe-CP, VHB Life sciences Inc.) in
the irrigating solution during cataract surgery, while Group 2
included patients who received vancomycin (20µg/ml) in the
irrigating solution during cataract surgery but did not receive
topical antibiotics preoperatively.

One hour preoperatively pupils were dilated using 1%
cyclopentolate (Cyclopent, Sun Pharmaceutical Ltd.) and 10%
phenylephrine (Drosyn, FDC Ltd.) eye-drops. Flurbiprofen
0.03% (Flur, Allergan India Pvt Ltd.) eye-drops were used
for sustained pupil dilatation. The eyes were anesthetized by
peribulbar block, using 6 ml mixture containing equal parts
of 0.5% bupivacaine [Bupivacaine hydrochloride, SPM drugs
Ltd.] and 2% lignocaine (Loxicard, Neon Laboratories Ltd.)
with 375 IU/ml of hyaluronidase (Omnidase, Sunways India
Pvt Ltd.) The eyelids, nose, cheek, eyebrow, and forehead were
scrubbed with 5% povidone-iodine (Aptidine-5, Appasamy
Ocular Devices Pvt Ltd.) for 3 min and with 70% alcohol for
another minute. Two drops of 5% povidone-iodine eye-drops
were instilled in the conjunctival sac 5 min before surgery.
A sterile drape with an adhesive foil was used to exteriorize
the eyelashes. All surgeries were performed by the same
surgeon (RS).

In both the groups, phacoemulsification was performed
through a 3.2-mm self-sealing superior scleral incision. Sterile
compound sodium lactate (Mount Mettur pharmaceuticals)
with epinephrine (Tidrenelene, Tamman Titoe Pharma Pvt Ltd.)
1:10,000 dilution (for infusion) and hydroxypropyl
methylcellulose (Appavisc PFS, Appasamy Ocular Devices
Pvt Ltd.) as viscoelastic material were used during the surgery.
However, in Group 2 patients, vancomycin (20µg/ml) was
added in the irrigating solution. After the surgery incision was
enlarged, a 5.25 mm, single-piece, polymethyl methacrylate
posterior chamber intraocular lens (Appalens, Appasamy
Ocular Devices Pvt Ltd.) was implanted in the bag. At the end
of the surgery, after the removal of all viscoelastic material,
0.2 ml of anterior chamber fluid was aspirated through the side
port incision with a 27–gauge cannula mounted on a tuberculin
syringe for the microbiological study. Only one microbiologist
was involved in the study for the purpose of analysis.

The aspirates collected from both the groups were treated
identically. They were inoculated onto blood agar, chocolate
agar, thioglycolate broth and Sabouraud dextrose agar. The
chocolate agar was incubated at 37°C in 5% carbon dioxide for
five days, and then incubated at 30°C without carbon dioxide
for an additional 10 days to study the fastidious organisms
before considering it to be negative. The thioglycolate broth
was incubated at 37°C aerobically for three weeks and sub-
cultured onto chocolate agar in 5% carbon dioxide and blood
agar anerobically. Sabouraud dextrose agar was incubated
aerobically at 37°C for 28 days before declaring it to be negative.
Colony characteristics and cell morphology were examined
under the microscope. The necessary biochemical tests were
conducted and the organisms were identified using standard
procedures.17 Antibiotic sensitivity was determined using broth
dilution method.18 Statistical analysis was carried out using
the Chi-square test.

Results

A total of 402 samples were taken from 402 eyes. Two eyes
were excluded from the study, as the aqueous humor was
inadequately collected and was realized later. Four hundred
eyes (of 400 patients) were enrolled in the study, of which
180 belonged to Group 1 and 220 eyes belonged to Group 2
respectively. The difference in the number of patients between
the two groups was due to the specific enrollment method
adopted. There were 240 men and 160 women. Patients were
in the age group of 30 to 78 years (average 57 years). The right
eye was operated in 212 patients (53%) and the left eye in 188
patients (47%).

Bacteria were cultured from AC aspirates in 38 out of 180
eyes (21.1%) in Group 1 and 17 out of 220 eyes (7.7%) in Group
2 (P = 0.001). Multiple organisms were identified in four eyes
(2.2%) in Group 1 while none of the eyes in Group 2 showed
multiple organisms. Coagulase-negative staphylococcus was the
most common organism isolated in both the groups. Eight
different bacteria were cultured in Group 1 and five in Group 2.
None of the eyes showed fungal contamination. The strains of
bacteria cultured from the AC aspirates are shown in Table 1.
Most of the isolated bacteria were sensitive to vancomycin,
with minimum inhibitory concentrations between 0.5 and
2.0 µg/ml.

None of the eyes had any intraoperative complication.
However, one patient in Group 1 developed endophthalmitis
postoperatively and the organism cultured from AC initially
during surgery as well as from intra-vitreal aspirate later
showed Alcaligenes faecalis. This patient responded to
intravitreal antibiotics, however, the final visual outcome
was poor due to consecutive optic atrophy. All patients were
followed up for a minimum of six months, with a range of
6 to 14 months (mean: 9.3 months).

Discussion

Despite technical improvements in cataract surgery,
endophthalmitis still remains the most dreaded complication of
intraocular surgery. Gram-positive organisms are responsible
for acute postoperative endophthalmitis in more than 90%
of cases. More than half of these are due to Staphylococcus
epidermidis infections, which may be due to its abundance
in the conjunctival flora.19 Conjunctival flora organisms are
responsible for postoperative endophthalmitis in the majority
of cases.20 Studies of DNA have shown that in Staphylococcus
epidermidis endophthalmitis, the most common source of
infection is the patient′s own flora.20

Ciprofloxacin and vancomycin are efficient against the gram-
positive organisms. Intraocular vancomycin has been shown
to be safe in doses up to 20 mg/l of vancomycin in irrigating
solution.16 The best choice for antimicrobial treatment of gram-
negative organisms is controversial. Aminoglycosides have
traditionally been recommended for gram-negative coverage.
Several clinical and laboratory reports have shown that
intravitreal aminoglycosides are toxic to the retina and retinal
pigment epithelium at doses close to the therapeutic level and
are thus avoided as a routine antibiotic in irrigating fluids.21

A study to evaluate the difference in the frequency of
endophthalmitis between two prophylactic regimens would
require thousands of cases to be statistically significant. As
a result, conclusions about efficacy in the prophylaxis of
endophthalmitis have frequently been based on the effect
of different regimen on conjunctival flora or intraocular
cultures obtained at the end of the surgery.13 Pospisil et al,
found two patients with postoperative endophthalmitis in
a study of 15 eyes with positive intraocular cultures but no
endophthalmitis in any of the 47 eyes with negative culture
results.22

The absence of clinical ocular infection in patients with
positive culture at the end of surgery attests to the small size of
inoculum and the ability of the AC to clear small bacterial loads.23
In an attempt to reduce the bacterial load from the conjunctival
flora, preoperative topical antibiotic is being practiced widely but
some studies have shown it to be of doubtful benefit clinically.24
Ta et al., showed no significant difference in AC contamination
between preoperative antibiotics of three days or one hour.24

In the present study, vancomycin was selected because
of its activity against pathogens that commonly cause
endophthalmitis and its safety in the form of prophylaxis.13,21 The appropriate antibiotic concentration and the time necessary
to effectively eliminate microorganisms after surgery are
unknown. The half-life of vancomycin in the AC has been
shown to be about two hours.11 Robert et al., reported that the
solutions in the AC at the end of surgery may be present for six
to eight hours, but no data are available about the duration of
effectiveness of antibiotic concentrations in the AC after being
used in irrigating solutions25 though a contact period of two
hours is recommended for the antibiotics to sterilize the AC.26
In our study, the contact period of organisms with vancomycin
was less than two hours in Group 2 patients, which might be the
reason for the aqueous aspirate showing growth of organisms,
despite some of them being sensitive to vancomycin.

The major limitations of this study are the small sample
size in both the groups, non-randomization in the selection of
the sample size, unequal sample size in the two groups. The
patients in the two groups were not enrolled simultaneously,
but there was a gap of 15 months between the initiation of
selection of patients in the two groups. Though this study
aims to prove the use of vancomycin in irrigating solution as
a prophylactic method for the prevention of endophthalmitis,
there is no direct relationship between AC contamination and
the endophthalmitis.13,20,24 Also, routine use of antibiotic may
lead to the emergence of resistance against vancomycin. The
US centers for Disease Control and Prevention have cautioned
against the generalized use of powerful antibiotics such as
vancomycin because of the emergence of vancomycin-resistant
strains of coagulase-negative staphylococcus and enterococcus.27

We conclude that the addition of vancomycin to the irrigation
solutions during uncomplicated phacoemulsification with
posterior chamber IOL implantation reduces the frequency of
positive intraocular cultures at the end of surgery as compared
to the ciprofloxacin eye drops used preoperatively. Additional
data about the selection of most appropriate antibiotic or
antibiotic combinations, dosage, safety and efficacy of this form
of treatment are needed before this prophylactic technique can
be routinely used during cataract surgery.

Notes

Source of Support: Nil

Conflict of Interest: None declared.

References

1.

Bohigian GM. A study of the incidence of culture-positive
endophthalmitis after cataract surgery in an ambulatory care
centerOphthalmic Surg Lasers 1999;30:295–8. [pmid: 10219034]